Use of parvovirus B19-like particles in self-illuminated photodynamic therapy for solid tumors.

Bioluminescence resonance energy transfer photodynamic therapy, which uses light generated by bioluminescent proteins to activate photosensitizers and produce reactive oxygen species without the need for external irradiation, has shown promising results in cancer models. However, the characterization of delivery systems that can incorporate the components of this therapy for preferential delivery to the tumor remains necessary. In this work, we have characterized parvovirus B19-like particles (B19V-VLPs) as a platform for a photosensitizer and a bioluminescent protein. By chemical and biorthogonal conjugation, we conjugated rose Bengal photosensitizer and firefly luciferase to B19V-VLPs and a protein for added specificity. The results showed that B19V-VLPs can withstand decoration with all three components without affecting its structure or stability. The conjugated luciferase showed activity and was able to activate rose Bengal to produce singlet oxygen without the need for external light. The photodynamic reaction generated by the functionalized VLPs-B19 can decrease the viability of tumor cells in vitro and affect tumor growth and metastasis in the 4 T1 model. Treatment with functionalized VLPs-B19 also increased the percentage of CD4 and CD8 cell populations in the spleen and in inguinal lymph nodes compared to vehicle-treated mice. Our results support B19V-VLPs as a delivery platform for bioluminescent photodynamic therapy components to solid tumors.

Encapsulated Rose Bengal Enhances the Photodynamic Treatment of Triple-Negative Breast Cancer Cells.

Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues.

Novel Photodynamic/Photothermal Treatment of Fungal Keratitis Using Rose Bengal-Loaded Polypyrrole-Gold Nanoparticles in Wistar Albino Rats.

Purpose: Fungal keratitis is a potential corneal contagious disease mainly caused by yeast such as Candida albicans and filamentous fungi such as Aspergillus niger. The response of fungal keratitis to standard antifungals is limited by the poor bioavailability, the limited ocular penetration of antifungal drugs, and the development of microbial resistance. Photodynamic therapy using rose bengal (RB) as a photosensitizer was found to be effective in fungal keratitis management; however, the hydrophilicity of RB limits its corneal penetration. Polypyrrole-coated gold nanoparticles (AuPpy NP) were introduced as a nano-delivery system of RB with high loading capacity. It was proved that (RB-AuPpy NP) exhibited a combined photodynamic/photothermal effect. This study aims to use the combined photodynamic/photothermal effect of RB-AuPpy NP as a novel protocol for treating Fungal Keratitis in albino Wistar rats. Methods: The rats were infected by C. albicans and A. niger. Each infected group of rats was subdivided into groups treated by RB followed by radiation (photodynamic only), AuPpy NP followed by radiation (photothermal only), and RB-AuPpy NP followed by radiation (combined photodynamic/photothermal). Histopathological examination and slit lamp imaging were done to investigate the results. Results: The results revealed that 3 weeks post-treatment, the corneas treated by RB-AuPpy NP (combined photodynamic/photothermal effect) exhibited the best improvement compared to other groups. Conclusion: This protocol can be considered a promising one for Fungal Keratitis management that overcomes microbial resistance problems.

Rose Bengal inhibits ß-amyloid oligomers-induced tau hyperphosphorylation via acting on Akt and CDK5 kinases.

RATIONALE: Tau hyperphosphorylation and aggregation is considered as a main pathological mechanism underlying Alzheimer's disease (AD). Rose Bengal (RB) is a synthetic dye used for disease diagnosis, which was reported to inhibit tau toxicity via inhibiting tau aggregation in Drosophila. However, it was unknown if RB could produce anti-AD effects in rodents. OBJECTIVES: The research aimed to investigate if and how RB could prevent ß-amyloid (Aß) oligomers-induced tau hyperphosphorylation in rodents. METHODS AND RESULTS: RB was tested in vitro (0.3-1 µM) and prevented Aß oligomers-induced tau hyperphosphorylation in PC12 cells. Moreover, RB (10-30 mg/kg, i.p.) effectively attenuated cognitive impairments induced by Aß oligomers in mice. Western blotting analysis demonstrated that RB significantly increased the expression of pSer473-Akt, pSer9-glycogen synthase kinase-3ß (GSK3ß) and reduced the expression of cyclin-dependent kinase 5 (CDK5) both in vitro and in vivo. Molecular docking analysis suggested that RB might directly interact with GSK3ß and CDK5 by acting on ATP binding sites. Gene Ontology enrichment analysis indicated that RB might act on protein phosphorylation pathways to inhibit tau hyperphosphorylation. CONCLUSIONS: RB was shown to inhibit tau neurotoxicity at least partially via inhibiting the activity of GSK3ß and CDK5, which is a novel neuroprotective mechanism besides the inhibition of tau aggregation. As tau hyperphosphorylation is an important target for AD therapy, this study also provided support for investigating the drug repurposing of RB as an anti-AD drug candidate.

PDT-active upconversion nanoheaters for targeted imaging guided combinatorial cancer phototherapies with low-power single NIR excitation.

A versatile nanoformulation is designed by anchoring human transferrin protein (Tf) on fluoromagnetic upconverting nanoheaters, NaGdF4:Yb,Er (UCNP), loaded with Rose Bengal (RB), for multimodal imaging guided synergistic photothermal (PTT) and photodynamic therapy (PDT) at the targeted tumor site. The NIR excitation of the UCNP-RB Forster Resonance Energy Transfer (FRET) pair results in the reactive oxygen species (ROS) generation for PDT, whereas the non-radiative transitions in Er result in the heat required for PTT. The intravenously injected theranostic agent (UCNP@Tf-RB) enabled; (1) combinatorial PTT and PDT of 4T1 tumors with minimal systemic toxicity, (2) dual targeted (passive and active) tumor accumulation, (3) dual-modal imaging (MRI/photothermal), and, (4) excellent stability and biocompatibility. The in vitro therapy data corroborates the MRI findings that Tf conjugation resulted in actively targeted tumor accumulation via over-expressed transferrin receptors (TfR) on 4T1 cells. Real-time photothermal imaging enabled visualization of the tumor while receiving the therapy. The UCNP@Tf-RB, for synergistic PTT-PDT, and UCNP@Tf, for PTT only, caused rapid suppression of tumor with a tumor-growth inhibition index (TGII) of ~0.91, and 0.79, respectively. Histopathological examination demonstrated minimal damage to non-targeted tissues and caused significant damage to the tumor. This theranostic methodology enhances anti-cancer therapeutic efficiency, and announces the potential for pre-clinical cancer therapy.

Histopathological Analysis of the Effect of Photodynamic Action on Post-Chemotherapy Excised Breast Cancer Tissue.

Background and objectives: Breast cancer is the most commonly diagnosed cancer in women and its mortality is increasing. Therefore, research to improve treatment is of paramount importance. One method of treatment is photodynamic therapy. Photodynamic therapy selectively stimulates apoptosis in photosensitizer-treated neoplastic breast cells as a result of cytotoxic singlet oxygen generation via collisions between triplet excited state photosensitizer and triplet ground state oxygen upon tissue irradiation. The aim of this study was to evaluate the effects of photodynamic action on cancerous breast tissue samples as a model of photodynamic therapy. Materials and Methods: Breast cancer tissue samples were obtained from post-operative material and the patterns of histopathological changes in breast cancer tissue before and after photodynamic action on post-chemotherapy tissue were evaluated. Excised tissue samples were obtained from 48 female breast cancer patients who had previously undergone chemotherapy. Breast cancer tissues for this study were taken from macroscopically visible tumors larger than 10 mm. Histopathological analysis was performed to evaluate any morphological changes prior to and after photodynamic action on the post-chemotherapy tissue samples. Eighteen breast cancer tissue samples were analyzed before chemotherapy, fifteen after chemotherapy, and fifteen samples were analyzed after chemotherapy and application of photodynamic action. The photosensitizer Rose Bengal was applied to the samples subjected to photodynamic action. Results: Photodynamic action on post-chemotherapy neoplastic tissue showed histological changes under a light microscope. The results showed that morphological changes in breast cancer tissues after chemotherapy and photodynamic action were dependent on the concentration of Rose Bengal. In all cases, follow-up imaging showed tumor shrinkage of an average of 35% from baseline size. Conclusions: Histopathological examination revealed photosensitizer-concentration-dependent changes after photodynamic action in excised post-chemotherapy tissue. The effects of photodynamic action observed in this study suggest that the application of photodynamic therapy after chemotherapy can aid in breast cancer cell eradication.

Gemini Surfactant Mediated Catansomes for Enhanced Singlet Oxygen Generation of Rose Bengal and Their Phototoxicity against Cancer Cells.

Photodynamic therapy (PDT) is an innovative technique for cancer treatment with minimal side effects, based on the use of a photosensitizer, oxygen, and light. Photosensitizers (PSs) have several limitations, that may limit their clinical use, like poor solubilization, self-aggregation, and lack of specific targeting, which can be addressed with the use of nanomaterials. Herein, a unique type of catansomes (CaSs) was prepared using a gemini imidazolium-based surfactant (1,3-bis[(3-octadecyl-1-imidazolio)methyl]benzene dibromide (GBIB) and a double chain surfactant, diaoctyl sodium sulfosuccinate or Aerosol OT (AOT). The formation of CaS GBIB/AOT was optimized in various ethanol/water (E/W) solvent ratios by employing a facile, quick, and most reliable solution-solution mixing method. The CaS was characterized by dynamic light scattering (DLS) and field emission gun scanning electron microscopy (FEG-SEM) techniques. The experimental results reveal that stable CaSs with a spherical shape were obtained at lower concentration (100 µM). Rose Bengal (RB), a PS of the xanthene family, was incorporated into these prepared CaSs, as proven by fluorescence spectroscopy, UV-visible absorption spectroscopy, and confocal laser scanning microscopy. Singlet oxygen (1O2) generation studies revealed the relevant role of the E/W solvent ratio as there was a 4-fold boost in the 1O2 production for GBIB/AOT in E/W = 50:50 and around 3-fold in E/W = 30:70. Also, the GBIB-rich 80:20 fraction was more efficient in increasing the 1O2 generation as compared to the AOT rich fraction (20:80). Further, their phototoxicity was tested in a water-rich solvent ratio (E/W = 30:70) against MCF-7 cells. Upon irradiation with a 532 nm laser (50 mW) for 5 min, RB@GBIB/AOT(20:80) fraction caused 50% decrease in the metabolic activity of MCF-7 cells, and RB@GBIB/AOT(80:20) fraction produced a maximum 85% decrease in cell viability. Furthermore, the enhancement in intracellular 1O2 generation by RB@GBIB/AOT, as compared to pure RB, was confirmed with singlet oxygen sensor green (SOSG). This new type of CaS based on gemini surfactants exhibiting a large amount of 1O2 generation, holds great interest for several applications, such as use in photomedicine in future.

Fabrication and characterization of chitosan nanoparticles using the coffee-ring effect for photodynamic therapy.

BACKGROUND AND OBJECTIVES: Biocompatible nanoparticles have been increasingly used in a variety of medical applications, including photodynamic therapy. Although the impact of synthesis parameters and purification methods is reported in previous studies, it is still challenging to produce a reliable protocol for the fabrication, purification, and characterization of nanoparticles in the 200-300 nm range that are highly monodisperse for biomedical applications. STUDY DESIGN/MATERIALS AND METHODS: We investigated the synthesis of chitosan nanoparticles in the 200-300 nm range by evaluating the chitosan to sodium tripolyphosphate (TPP) mass ratio and acetic acid concentration of the chitosan solution. Chitosan nanoparticles were also crosslinked to rose bengal and incubated with human breast cancer cells (MCF-7) to test photodynamic activity using a green laser (λ = 532 nm, power = 90 mW). RESULTS: We established a simple protocol to fabricate and purify biocompatible nanoparticles with the most frequent size occurring between 200 and 300 nm. This was achieved using a chitosan to TPP mass ratio of 5:1 in 1% v/v acetic acid at a pH of 5.5. The protocol involved the formation of nanoparticle coffee rings that showed the particle shape to be spherical in the first approximation. Photodynamic treatment with rose bengal-nanoparticles killed ~98% of cancer cells. CONCLUSION: A simple protocol was established to prepare and purify spherical and biocompatible chitosan nanoparticles with a peak size of ~200 nm. These have remarkable antitumor activity when coupled with photodynamic treatment.

Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies.

Rose bengal has been used in the diagnosis of ophthalmic disorders and liver function, and has been studied for the treatment of solid tumor cancers. To date, the antibacterial activity of rose bengal has been sporadically reported; however, these data have been generated with a commercial grade of rose bengal, which contains major uncontrolled impurities generated by the manufacturing process (80-95% dye content). A high-purity form of rose bengal formulation (HP-RBf, >99.5% dye content) kills a battery of Gram-positive bacteria, including drug-resistant strains at low concentrations (0.01-3.13 µg/mL) under fluorescent, LED, and natural light in a few minutes. Significantly, HP-RBf effectively eradicates Gram-positive bacterial biofilms. The frequency that Gram-positive bacteria spontaneously developed resistance to HP-RB is extremely low (less than 1 × 10-13). Toxicity data obtained through our research programs indicate that HP-RB is feasible as an anti-infective drug for the treatment of skin and soft tissue infections (SSTIs) involving multidrug-resistant (MDR) microbial invasion of the skin, and for eradicating biofilms. This article summarizes the antibacterial activity of pharmaceutical-grade rose bengal, HP-RB, against Gram-positive bacteria, its cytotoxicity against skin cells under illumination conditions, and mechanistic insights into rose bengal's bactericidal activity under dark conditions.

Rose Bengal and Future Directions in Larynx Tumor Photodynamic Therapy.

Photodynamic Therapy (PDT) seems to be a promising method in the treatment of larynx tumor tissues. The aim of the present analysis was the study of photosensitizer penetration of larynx tissue associated with the application of PDT in vitro. This study is based on the use of photosensitive compounds Rose Bengal (RB) that selectively accumulate in larynx tissue. The selection of the study group of patients who will undergo surgery in accordance with medical principles was of key importance for the project. Histopathological examination of samples subjected to PDT revealed numerous changes in the morphology of the cancer cells and surrounding tissues. After PDT treatment, the number of tumor cells decreased compared with the cells number before PDT and the arrangement was relatively loose. After PDT with RB the nuclei morphology was incomplete and fragmented. The effects of the applied PDT of larynx in vitro were assessed under an optical microscope. The future directions in larynx tumor PDT with the use of upconversion nanoparticles (UPCNP) is also discussed.

Intralesional injection of rose bengal augments the efficacy of gemcitabine chemotherapy against pancreatic tumors.

BACKGROUND: Chemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study aims to explore combination therapies that could boost the efficacy of standard of care regimens in pancreatic cancer patients. METHODS: In this study, we used PV-10, a 10% solution of rose bengal, to induce the death of human pancreatic tumor cells in vitro. Murine in vivo studies were carried out to examine the effectiveness of the direct injection of PV-10 into syngeneic pancreatic tumors in causing lesion-specific ablation. Intralesional PV-10 treatment was combined with systemic gemcitabine treatment in tumor-bearing mice to investigate the control of growth among treated tumors and distal uninjected tumors. The involvement of the immune-mediated clearance of tumors was examined in immunogenic tumor models that express ovalbumin (OVA). RESULTS: In this study, we demonstrate that the injection of PV-10 into mouse pancreatic tumors caused lesion-specific ablation. We show that the combination of intralesional PV-10 with the systemic administration of gemcitabine caused lesion-specific ablation and delayed the growth of distal uninjected tumors. We observed that this treatment strategy was markedly more successful in immunogenic tumors that express the neoantigen OVA, suggesting that the combination therapy enhanced the immune clearance of tumors. Moreover, the regression of tumors in mice that received PV-10 in combination with gemcitabine was associated with the depletion of splenic CD11b+Gr-1+ cells and increases in damage associated molecular patterns HMGB1, S100A8, and IL-1α. CONCLUSIONS: These results demonstrate that intralesional therapy with PV-10 in combination with gemcitabine can enhance anti-tumor activity against pancreatic tumors and raises the potential for this strategy to be used for the treatment of patients with pancreatic cancer.

Local and regional therapy for primary and locally recurrent melanoma.

In the vast majority of cases, cutaneous melanoma presents as localized disease and is treated with wide excision and sentinel lymph node biopsy, with shared decision making regarding completion lymph node dissection and adjuvant systemic therapy. The treatment of recurrent and in-transit disease is more complex, with further options for regional and systemic therapies and multiple variables to be factored into decisions. Rates of overall and complete response to regional therapies can be quite high in carefully chosen patients, which limits the need for systemic therapies and their inherent side effects. Ongoing trials aim to assess the efficacy of combination regional and systemic therapies and assist in deciding among these options. This review discusses the treatment of primary melanoma and regional nodal disease and offers an in-depth discussion of options for the treatment of recurrent melanoma and in-transit melanoma.

Development of Glycerol-Rose Bengal-Polidocanol (GRP) foam for enhanced sclerosis of a cyst for cystic diseases.

Polycystic kidney disease (PKD) is a common genetic disorder that results in a proliferating and enlarging cyst and ultimately leads to loss of kidney function. Because an enlarged cyst is a primary factor for limited kidney function, the large cyst is surgically removed by laparoscopic deroofing or sclerosant. This a relatively nascent treatment method entails complications and sometimes fail due to the cyst fluid refilling and infection. This study proposes using a more stable and effective polidocanol foam with glycerol and Rose Bengal (GRP form) to prevent cyst regeneration and irritation, which is caused by the required body movement during the treatment. Specifically, the foam retention time and viscosity were increased by adding glycerol up to 10% (w/v). The GRP form inhibited cellular proliferation and disrupted cellular junctions, e-cadherin, and cyst formation, demonstrated by the LDH, Live and Dead, and re-plating culture assays. The GRP foam was shown to be a safe and effective treatment as a commercial grade polidocanol foam form by an in vivo study in which subcutaneously injected mice injected with commercial 3% polidocanol, and the GRP foam showed no difference in inflammation. Thus, this study provides an advanced polidocanol form by adding glycerol and Rose-Bengal to help existing sclerotherapy.

Iontophoresis-Assisted Rose Bengal and Green Light Corneal Cross-Linking.

PURPOSE: To evaluate the effects of the application of iontophoresis-assisted rose bengal and green light cross-linking (I-RGX) therapy on enucleated rabbit eyes for corneal biomechanical parameters, dye diffusion rates, and green light levels reaching deep tissues and to compare these parameters with a standard rose bengal and green light cross-linking (RGX) therapy. METHOD: Forty-five enucleated rabbit eyes were used in this study. To evaluate biomechanical changes, corneas were divided into the following 4 groups: the control group, the 0.1% rose bengal application group, the RGX group (100 J/cm), and the I-RGX group (100 J/cm). After this, corneal strips were evaluated with a uniaxial extensometer. To assess corneal dye diffusion, postprocedure dye depth was recorded with anterior segment optic coherence tomography. The amount of irradiation passing through the cornea during irradiation with 250 mW/cm irradiation power was measured with a laser power meter at the first, third, and seventh minutes. RESULTS: In the I-RGX-treated group especially, the mean elastic modulus and corneal stiffness values were about 4.7 times higher when compared with the controls and about 2.2 times higher than those in the RGX group. The rose bengal diffusion depth was 26.63% ± 3.84% of the total corneal thickness in the rose bengal drop group, but this value increased to 42.22% ± 4.77% in the iontophoresis group (<0.001). After iontophoresis, an average of 98% of the 100 J/cm green light was kept in the cornea. CONCLUSIONS: I-RGX is a very useful method for increasing corneal biomechanical strength and is highly effective in increasing the amount of corneal dye diffusion into the cornea while also minimalizing the amount of laser passage reaching deeper tissues.

Rose Bengal-Amphiphilic Peptide Conjugate for Enhanced Photodynamic Therapy of Malignant Melanoma.

Malignant melanoma is an aggressive skin cancer with poor survival outcomes for patients diagnosed at an advanced stage. While targeted serine/threonine-protein kinase B-Raf (BRAF) and immune checkpoint inhibitors have improved survival outcomes for a proportion of these patients, response rates remain variable. There is a need, therefore, for more effective treatments to bolster the options available for melanoma patients. In this manuscript, we covalently attached Rose Bengal (RB) to the amphipathic peptide (AMP) C(KLAKLAK)2 and determined the effectiveness of the resulting RB-C(KLAKLAK)2 conjugate as a photodynamic therapy (PDT) sensitizer. RB-C(KLAKLAK)2-mediated PDT treatment of subcutaneous B16-F10-Luc2 tumors in C57 mice resulted in lesions that were 479% smaller at the end of the study than animals treated with RB-mediated PDT. The synergistic effect between RB and C(KLAKLAK)2 has been attributed to the AMP sensitizing cells to reactive oxygen species (ROS), making them more susceptible to ROS-induced oxidative stress.

Comparison of Photochemical Crosslinking Versus Sutures for Bonding Conjunctival Grafts.

BACKGROUND AND OBJECTIVES: To explore whether Rose Bengal-induced photochemical crosslinking (RB-PCL) can be a replacement for sutures in conjunctival autograft bonding, we compared the safety, operating time, postoperative ocular signs, and inflammatory responses of RB-PCL versus nylon suturing for sealing conjunctival autografts in rabbits. STUDY DESIGN/MATERIALS AND METHODS: Thirty-six New Zealand White rabbits underwent limbal conjunctival autografting using either sutures or RB-PCL to attach conjunctival autografts to the bare sclera. Animals were randomized to one of two groups (18 per group): the suture group or RB-PCL group. Photochemical crosslinking with a wavelength of 532 nm green light with an illumination intensity of 0.6 W/cm2 for 250 seconds (150 J/cm2 ) or suturing was performed followed by light examination at 3, 7, 28 days after surgery to evaluate the healing condition. Rabbits in each group were euthanized on day 3 (n = 6), 7 (n = 6), or 28 (n = 6) postoperatively, and the graft tissues from the surgical site were processed to evaluate inflammatory response by assessing protein levels of tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) as well as histological examination. Cell viability was evaluated by counting both total and dead cells on hematoxylin and eosin (H&E) stained tissue samples from both groups at 3 and 7 days after surgery. The surgery procedure time was recorded and the graft surface temperatures were measured before and after illumination. RESULTS: Photochemical crosslinking effectively secured the limbal conjunctival autograft over an ocular conjunctival defect with no significant difference from the suture group. The time required for this light activated bonding method was ~550 seconds in comparison with the suture method of half hour. The differences of measured temperature on the graft surface before and after RB-PCL treatment were 2.98 ± 0.11°C. The induction of IL-6 and TNF-α protein was remarkably reduced in the RB-PCL group compared with the suture group at 3 and 7 days after surgery. Histology revealed less infiltrated neutrophils were observed in the RB-PCL group than in the suture group at 3 and 7 days postoperatively. Furthermore, the RB-PCL group showed a better healing process with less eye discharge and mild conjunctival congestion. No significant difference in percent dead cells was observed between RB-PCL and suture groups at 3 and 7 days after surgery. CONCLUSIONS: RB-PCL is a promising alternative for bonding the conjunctival autograft with shorter operation time, less inflammation and better healing outcomes compared to conventional suture. Thermal damage and phototoxicity were not observed using the RB-PCL method in bonding conjunctival grafts. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Upconversion System with Quantum Dots as Sensitizer: Improved Photoluminescence and PDT Efficiency.

Upconversion nanoparticles (UCNPs) are prospective platforms for bioimaging and phototherapy, but a critical bottleneck is the limited brightness due to the faint absorptivity of lanthanide ions and the low quantum yield. To circumvent this problem, we herein propose our strategy to reconstruct the energy cascade of UCNPs using semiconductor quantum dots (QDs) as light sensitizer of Nd3+/Yb3+ codoped UCNPs. Ag2Se QDs with strong absorption at 808 nm acted as efficient antenna and transferred their energy to Yb3+ via a resonance energy transfer process, significantly enhancing the luminescence of UCNPs. This nanocomposite was then combined with Rose Bengal and applied for photodynamic therapy. Both in vitro and in vivo studies revealed the introduction of QDs improved the therapeutic performance remarkably. Our study suggests Ag2Se QDs with excellent photophysical properties can be promising agents to overcome the shortcomings of UCNPs and further strengthen their applications.

Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study.

PURPOSE: To report clinical outcomes of rose bengal photodynamic antimicrobial therapy (RB-PDAT) as an adjunct treatment for severe, progressive infectious keratitis. DESIGN: Consecutive interventional case series. METHODS: Patients with progressive infectious keratitis unresponsive to standard medical therapy underwent RB-PDAT at the Bascom Palmer Eye Institute from January 2016 through March 2018. RB-PDAT was performed by applying a solution of rose bengal (0.1% or 0.2% RB in balanced salt solution) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm2 custom-made green LED source for 15 minutes (5.4 J/cm2). RESULTS: The current study included 18 patients (7 male and 11 female) ranging from 17 to 83 years old. Acanthamoeba was the most frequent microbe (10/17; 59%), followed by Fusarium spp. (4/17; 24%), Pseudomonas aeruginosa (2/17; 12%), and Curvularia spp. (1/17; 6%); 1 patient had no confirmed microbiologic diagnosis. Main clinical risk factor for keratitis included contact lens wear (79%). The average area of epithelial defect prior to first RB-PDAT was 32 ± 27 mm2 and average stromal depth hyperreflectivity measured with anterior segment optical coherence tomography was 269 ± 75 µm. Successful RB-PDAT (avoidance of therapeutic keratoplasty) was achieved in 72% of the cases, with an average time to clinical resolution (decreased pain and inflammation with re-epithelialization and infiltrate resolution) of 46.9 ± 26.4 days after RB-PDAT. Time of follow-up after RB-PDAT was 13.3 ± 5.7 months. CONCLUSION: RB-PDAT can be considered as an adjunct therapy for cases of severe, progressive infectious keratitis before performing a therapeutic keratoplasty.

Self-assembled peptido-nanomicelles as an engineered formulation for synergy-enhanced combinational SDT, PDT and chemotherapy to nasopharyngeal carcinoma.

A formulation of self-assembled peptido-nanomicelles has been developed for a combinational treatment of SDT, PDT and chemotherapy to nasopharyngeal carcinoma. In vitro cellular tests and in vivo mice therapy proved effective for targeted tumor growth inhibition. These merits provided a novel approach to non-invasive cancer treatments.